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Chemoprevention of esophageal adenocarcinoma in a rat model by ursodeoxycholic acid

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Abstract

Reflux of bile acid into the esophagus induces esophagitis, inflammation-stimulated hyperplasia, metaplasia such as Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC). Caudal-type homeobox 2 (Cdx2) via nuclear factor (NF)-κB induced by bile acid is an important factor in the development of BE and EAC. In colorectal cancer, experimental data suggest a chemopreventive effect of ursodeoxycholic acid (UDCA). We hypothesized that UDCA may protect against the esophageal inflammation–metaplasia–carcinoma sequence by decreasing the overall proportion of the toxic bile acids. Wistar male rats that underwent a duodenoesophageal reflux procedure were divided into two groups. One group was given commercial chow (control group), and the other was given experimental chow containing UDCA (UDCA group). The animals were killed at 40 weeks after surgery, and their bile and esophagus were examined. In the UDCA group, the esophagitis was milder and the incidence of BE was significantly lower (p < 0.05) than in the control group, and EAC was not observed (p < 0.05). In analysis of the compartment of bile acid, UDCA was markedly increased in the UDCA group compared with the control group (32.7 ± 11.4 vs. 0.82 ± 0.33 mmol/L, p < 0.05) and cholic acid was decreased (32.7 ± 4.05 vs. 60.9 ± 8.26 mmol/L, p < 0.05). Expression intensity of Cdx2 and NF-κB was greater in the control group than in the UDCA group (p < 0.05). UDCA may be a chemopreventive agent against EAC by varying the bile acid composition.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterologic Surgery, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Eisuke Ojima, Takashi Fujimura, Katsunobu Oyama, Tomoya Tsukada, Jun Kinoshita, Tomoharu Miyashita, Hidehiro Tajima, Sachio Fushida & Tetsuo Ohta

  2. Center for Biomedical Research, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan

    Shin-ichi Harada

  3. Department of Pathology, Shiga University of Medical Science, Ohtsu, Shiga, 520-2192, Japan

    Ken-ichi Mukaisho & Takanori Hattori

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  1. Eisuke Ojima
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  2. Takashi Fujimura
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  3. Katsunobu Oyama
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  4. Tomoya Tsukada
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  5. Jun Kinoshita
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  12. Tetsuo Ohta
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Correspondence to Takashi Fujimura.

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Ojima, E., Fujimura, T., Oyama, K. et al. Chemoprevention of esophageal adenocarcinoma in a rat model by ursodeoxycholic acid. Clin Exp Med 15, 343–350 (2015). https://doi.org/10.1007/s10238-014-0301-x

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  • DOI: https://doi.org/10.1007/s10238-014-0301-x

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